Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-α and granulocyte colony-stimulating factor in bronchial epithelium: Implications for airway inflammation in cystic fibrosis

Florencia McAllister, Adam Henry, James L. Kreindler, Patricia J. Dubin, Lauren Ulrich, Chad Steele, Jonathan Finder, Joseph M. Pilewski, Beatriz M. Carreno, Samuel J. Goldman, Jaana Pirhonen, Jay K. Kolls

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Abstract

IL-17R signaling is critical for pulmonary neutrophil recruitment and host defense against Gram-negative bacteria through the coordinated release of G-CSF and CXC chemokine elaboration. In this study, we show that IL-17R is localized to basal airway cells in human lung tissue, and functional IL-17R signaling occurs on the basolateral surface of human bronchial epithelial (HBE) cells. IL-17A and IL-17F were potent inducers of growth-related oncogene-α and G-CSF in HBE cells, and significant synergism was observed with TNF-α largely due to signaling via TNFRI. The activities of both IL-17A and IL-17F were blocked by a specific anti-IL-17R Ab, but only IL-17A was blocked with a soluble IL-17R, suggesting that cell membrane IL-17R is required for signaling by both IL-17A and IL-17F. Because IL-17A and IL-17F both regulate lung neutrophil recruitment, we measured these molecules as well as the proximal regulator IL-23p19 in the sputum of patients with cystic fibrosis (CF) undergoing pulmonary exacerbation. We found significantly elevated levels of these molecules in the sputum of patients with CF who were colonized with Pseudomonas aeruginosa at the time of pulmonary exacerbation, and the levels declined with therapy directed against P. aeruginosa. IL-23 and the downstream cytokines IL-17A and IL-17F are critical molecules for proinflammatory gene expression in HBE cells and are likely involved in the proinflammatory cytokine network involved with CF pathogenesis.

Original languageEnglish (US)
Pages (from-to)404-412
Number of pages9
JournalJournal of Immunology
Volume175
Issue number1
StatePublished - Jul 1 2005

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Interleukin-17 Receptors
Interleukin-17
Granulocyte Colony-Stimulating Factor
Oncogenes
Cystic Fibrosis
Epithelium
Inflammation
Growth
Lung
Neutrophil Infiltration
Epithelial Cells
Sputum
Pseudomonas aeruginosa
Interleukin-23 Subunit p19
Cytokines
Interleukin-23
CXC Chemokines
Gram-Negative Bacteria

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-α and granulocyte colony-stimulating factor in bronchial epithelium : Implications for airway inflammation in cystic fibrosis. / McAllister, Florencia; Henry, Adam; Kreindler, James L.; Dubin, Patricia J.; Ulrich, Lauren; Steele, Chad; Finder, Jonathan; Pilewski, Joseph M.; Carreno, Beatriz M.; Goldman, Samuel J.; Pirhonen, Jaana; Kolls, Jay K.

In: Journal of Immunology, Vol. 175, No. 1, 01.07.2005, p. 404-412.

Research output: Contribution to journalArticle

McAllister, F, Henry, A, Kreindler, JL, Dubin, PJ, Ulrich, L, Steele, C, Finder, J, Pilewski, JM, Carreno, BM, Goldman, SJ, Pirhonen, J & Kolls, JK 2005, 'Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-α and granulocyte colony-stimulating factor in bronchial epithelium: Implications for airway inflammation in cystic fibrosis', Journal of Immunology, vol. 175, no. 1, pp. 404-412.
McAllister, Florencia ; Henry, Adam ; Kreindler, James L. ; Dubin, Patricia J. ; Ulrich, Lauren ; Steele, Chad ; Finder, Jonathan ; Pilewski, Joseph M. ; Carreno, Beatriz M. ; Goldman, Samuel J. ; Pirhonen, Jaana ; Kolls, Jay K. / Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-α and granulocyte colony-stimulating factor in bronchial epithelium : Implications for airway inflammation in cystic fibrosis. In: Journal of Immunology. 2005 ; Vol. 175, No. 1. pp. 404-412.
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T2 - Implications for airway inflammation in cystic fibrosis

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AU - Henry, Adam

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AU - Ulrich, Lauren

AU - Steele, Chad

AU - Finder, Jonathan

AU - Pilewski, Joseph M.

AU - Carreno, Beatriz M.

AU - Goldman, Samuel J.

AU - Pirhonen, Jaana

AU - Kolls, Jay K.

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